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Pathogenesis and autoimmunity initiated by a viral protein-induced apoptotic bodies
(2016)
huomattavasti ApoBodikonsentraation myötä. Nämä löydökset tukevat hypoteesia. B19 NS1 ApoBodit tarjoavat elimistölle itseantigeenejä, johon immuunipuolustus reagoi ja näin ollen autoimmuniteetti saa alkunsa. Tämä tutkimus tarjoaa mekanismin B19 osallisuudesta...
Human parvovirus B19 (B19) is a widespread virus that infects people of all ages. In children, it usually causes an erythema infectiosum, a rash illness called the Fifth disease. In adults, it can cause arthralgia, arthritis, different types of anemia, and hydrops fetalis in pregnant women. Furthermore, the infection can lead to severe autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, myocarditis, liver, and kidney diseases. However, the B19 infection can sometimes be asymptomatic. The exact mechanisms by which B19 contributes to autoimmune diseases are still not known. However, the non-structural protein 1 (NS1) of B19 is known as a cytotoxic protein that induces apoptosis in host cells, thus forming apoptotic bodies (ApoBods) that contain self-antigens along with viral NS1 protein. Mice were used as a model organism in this study to investigate the effects of the NS1 ApoBods in vivo. It was hypothesized that the ApoBods initiate an SLE-like autoimmune disease in mice which manifests itself as autoantibody production, immune cell infiltration into the tissues, and tissue damage. Mice were inoculated with 25 µg, 50 µg, and 100 µg of B19 NS1 induced ApoBods. Blood was collected from the mice at week one, and four, before booster injections were administrated. At week eight, the mice were euthanized, blood was collected and serum isolated. Brain, heart, kidneys, liver, and spleen were dissected from each mouse for histopathological analysis. Sections embedded in paraffin, and stained with hematoxylin and eosin were studied for morphological and pathological changes with bright-field microscopy. Presence of anti-double-stranded DNA antibodies was investigated with a commercial Crithidia luciliae immunofluorescence test, and with a newly developed enzyme-linked immunosorbent assay. Anti-double-stranded DNA antibodies, which are the signature biomarker of SLE, were detected with both methods in the mice inoculated with B19 NS1 ApoBods. Immune cell infiltrates were detected in the kidneys, heart, and liver of the mice. In addition, neuronal degeneration was detected in the brain of all the mice treated with B19 NS1 ApoBods, and suspected demyelination was seen in the brain of the mice treated with 50 µg, and 100 µg of B19 NS1 ApoBods. Myocardial disarray was observed in the hearts of these two groups. Furthermore, in the hearts of all mice treated with B19 NS1 ApoBods, myocardial degeneration was detected. In the spleen of mice treated with 50 µg of the ApoBods, germinal centers had formed. Moreover, the proportion of the white pulp in the spleen was significantly increased by the dosage of ApoBods. These findings supported the hypothesis. B19 NS1 ApoBods cause inflammation by providing self-antigens to which the immune system reacts, and autoimmunity is initiated. Hence, this study provided a mechanism of B19 involvement in the pathogenesis of autoimmune diseases. Furthermore, this mechanism and model are applicable to studies of other viruses, such as cytomegalovirus and Epstein-Barr....
Human parvovirus B19 (B19) is a widespread virus that infects people of all ages. In children, it usually causes an erythema infectiosum, a rash illness called the Fifth disease. In adults, it can cause arthralgia, arthritis, different types of anemia, and hydrops fetalis in pregnant women. Furthermore, the infection can lead to severe autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, myocarditis, liver, and kidney diseases. However, the B19 infection can sometimes be asymptomatic. The exact mechanisms by which B19 contributes to autoimmune diseases are still not known. However, the non-structural protein 1 (NS1) of B19 is known as a cytotoxic protein that induces apoptosis in host cells, thus forming apoptotic bodies (ApoBods) that contain self-antigens along with viral NS1 protein. Mice were used as a model organism in this study to investigate the effects of the NS1 ApoBods in vivo. It was hypothesized that the ApoBods initiate an SLE-like autoimmune disease in mice which manifests itself as autoantibody production, immune cell infiltration into the tissues, and tissue damage. Mice were inoculated with 25 µg, 50 µg, and 100 µg of B19 NS1 induced ApoBods. Blood was collected from the mice at week one, and four, before booster injections were administrated. At week eight, the mice were euthanized, blood was collected and serum isolated. Brain, heart, kidneys, liver, and spleen were dissected from each mouse for histopathological analysis. Sections embedded in paraffin, and stained with hematoxylin and eosin were studied for morphological and pathological changes with bright-field microscopy. Presence of anti-double-stranded DNA antibodies was investigated with a commercial Crithidia luciliae immunofluorescence test, and with a newly developed enzyme-linked immunosorbent assay. Anti-double-stranded DNA antibodies, which are the signature biomarker of SLE, were detected with both methods in the mice inoculated with B19 NS1 ApoBods. Immune cell infiltrates were detected in the kidneys, heart, and liver of the mice. In addition, neuronal degeneration was detected in the brain of all the mice treated with B19 NS1 ApoBods, and suspected demyelination was seen in the brain of the mice treated with 50 µg, and 100 µg of B19 NS1 ApoBods. Myocardial disarray was observed in the hearts of these two groups. Furthermore, in the hearts of all mice treated with B19 NS1 ApoBods, myocardial degeneration was detected. In the spleen of mice treated with 50 µg of the ApoBods, germinal centers had formed. Moreover, the proportion of the white pulp in the spleen was significantly increased by the dosage of ApoBods. These findings supported the hypothesis. B19 NS1 ApoBods cause inflammation by providing self-antigens to which the immune system reacts, and autoimmunity is initiated. Hence, this study provided a mechanism of B19 involvement in the pathogenesis of autoimmune diseases. Furthermore, this mechanism and model are applicable to studies of other viruses, such as cytomegalovirus and Epstein-Barr....
Fungal Dysbiosis and Intestinal Inflammation in Children With Beta-Cell Autoimmunity
(Frontiers Media, 2020)
of intestinal inflammation, namely fecal human beta-defensin-2 (HBD2), calprotectin and secretory total IgA, were performed. Anti-Saccharomyces cerevisiae antibodies (ASCA) and circulating cytokines, IFNG, IL-17 and IL-22, were studied. After these analyses...
Parvovirus B19V Nonstructural Protein NS1 Induces Double-Stranded Deoxyribonucleic Acid Autoantibodies and End-Organ Damage in Nonautoimmune Mice
(Oxford University Press, 2019)
Background
Viral infection is implicated in development of autoimmunity. Parvovirus B19 (B19V) nonstructural protein, NS1, a helicase, covalently modifies self double-stranded deoxyribonucleic acid (dsDNA) and induces ...
Human Parvovirus B19 Induced Apoptotic Bodies Contain Altered Self-Antigens that are Phagocytosed by Antigen Presenting Cells.
(Public Library of Science, 2013)
Human parvovirus B19 (B19V) from the erythrovirus genus is known to be a pathogenic virus in humans. Prevalence of B19V infection has been reported worldwide in
all seasons, with a high incidence in the spring. B19V is ...
Pathogenic mechanisms of how human parvovirus breaks self-tolerance
(University of Jyväskylä, 2017)
It is known that viral infections can cause acute, chronic, and autoimmune diseases
(ADs). However, the mechanism of how a persistent viral infection contributes to ADs
remains still unclear. In this thesis, pathological ...
Fyysisen aktiivisuuden yhteys suolistomikrobistoon
(2023)
Suolistomikrobiston koostumuksen ja sen monimuotoisuuden on havaittu olevan yhteydessä
terveyteen ja sairauksiin. Lisäksi on esitetty, että suolistomikrobiston monimuotoisuutta
voitaisiin yleisesti ottaen pitää yhtenä ...
Sosiaalisen nousu ja paljas elämä : Arendt suhteessa Foucault'n ja Agambenin edustamaan biopolitiikan teoriaperinteeseen
(2016)
Tutkielman tarkoituksena on vertailla Hannah Arendtin poliittista ajattelua biopolitiikan kahden keskeisen teoreetikon Michel Foucault’n ja Giorgio Agambenin ajatteluun. Arendt analysoi sosiaalisen nousua, jonka yhteydessä ...